The cellular vehicles of "natural resistance" to oncogenesis are largely unknown. However, there are indications that they may reside in the lymphohemopoietic and immune systems. The objective of this project is to study whether resistance to oncogenesis can be passively conferred by transplantation of bone marrow from a tumor-resistant donor to a tumor-susceptible host. A new system for transplantation of allogeneic and xenogeneic, histoincompatible bone marrow has been developed recently. It is based on the use of unmanipulated bone marrow and of an ultrafiltration fraction of MW greater than 100.000 called "marrow regulating factor" (MRF) which has been separated from bone marrow cell suspensions supernatants. When administered together with "washed" bone marrow cells, this fraction promotes the engraftment of allogeneic marrow and permanent, GVHD-free chimerism in H-2 incompatible mice. The timing and dosage of administration of MRF depends closely on the H-2 character of donor and recipient (mice, rats, rabbits). MRF is not species-specific. MRF seems to promote, by a still unknown mechanism, a rapid and balanced engraftment of allogeneic marrow and enduring chimerism (over one year after transplantation) with no early or late symptoms of GVHD. We intend to apply this new method to mice developing spontaneous lymphosarcoma (AKR) or mammary carcinoma (C3H). Bone marrow cells harvested from tumor-resistant mice (e.g. C57BL/6) will be transplanted into the tumor-susceptible mice. Conversely, C57BL/6 mice will be transplanted with bone marrow from AKR/Cu or C3H/He mice. Maintenance, completeness and duration of chimerism will be followed in the individual animals together with genesis and/or evoluation of the tumors. The system developed is based on a combination of earlier and recent studies in transplantation and cell immunology, hematology and cancer research. Its implications for the clinical application of BMT to cancer therapy are implicit.